Background
Sex chromosome aneuploidies (SCAs) are a collectively common family of genetic disorders that increase risk for neuropsychiatric and cognitive impairment. Beyond being important medical disorders in their own right, SCAs also offer a unique naturally-occurring model for X- and Y-chromosome influences on the human brain. However, it remains unclear if (i) different SCAs are associated with different profiles of psychopathology, and (ii) the notable interindividual variation in psychopathology is related to co-occurring variation in cognitive ability.
Methods
We examined scores for 11 dimensions of psychopathology [Child/Adult Behavior Checklist (CBCL)] and general cognitive ability [full-scale IQ (FSIQ) from Wechsler tests] in 110 youth with varying SCAs (XXY = 41, XYY = 22, XXX = 27, XXYY = 20) and 131 typically developing controls (XX = 59, XY = 72).
Results
All SCAs were associated with elevated CBCL scores across several dimensions of psychopathology, but social and attentional functioning were particularly sensitive to carriage of a supernumerary Y-chromosome. There was marked variability in CBCL scores within each SCA group, which generally correlated negatively with IQ, but most strongly so for social and attentional difficulties. These correlations showed subtle differences as a function of SCA group and CBCL scale.
Conclusions
There is domain-specific variation in psychopathology across SCA groups, and domain-specific correlation between psychopathology and IQ within SCAs. These findings (i) help to tailor clinical assessment of this common and impactful family of genetic disorders, and (ii) suggest that dosage abnormalities of X- and Y-linked genes impart somewhat distinct profiles of neuropsychiatric risk.